Hormone Test Research Articles

Why do patients with pheochromocytomas/paragangliomas exhibit significantly inconsistent elevation of catecholamines and their metabolites? a large Chinese cohort study.

Inconsistent elevation of catecholamines (CAs) and metanephrines (MNs) was observed in pheochromocytomas/paragangliomas (PPGLs). This study aimed to explore its potential causes and report the diagnostic efficacy of MNs and CAs in a large Chinese PPGL cohort. Clinical data and results of hormone tests were retrospectively collected. The sensitivity of plasma MNs and 24h-urinary CAs was analyzed. Clinical characteristics were compared between patients with positive and negative biochemical results, and among those with inconsistent elevation of MNs and CAs. Seven hundred and three patients were included, with a median onset age of 41.0 years. Plasma MNs (93% ~ 99%) showed prior diagnostic sensitivity to 24h-urinary CAs (74% ~ 89%). Patients with negative biochemical results presented as a smaller tumor (1.7 cm vs. 4.3 cm, P = 0.001), a higher proportion of normal blood pressure (60.0% vs. 20.5%, P = 0.002) and negative 131I-meta-iodobenzylguanidine (131I-MIBG) imaging (55.6% vs. 17.3%, P = 0.012). An earlier age of onset (40.0 vs. 41.0 vs. 44.5 years, P = 0.025), a higher proportion of paroxysmal hypertension (36.5% vs. 29.2% vs. 32.2%, P = 0.005) and the Epinephrine secretion type (79.3% vs. 37.7% vs. 48.0%, P < 0.001) were found in patients with the ratio of MNs/CAs elevation multiples <0.5 than those with the ratio between 0.5 and 2 or >2. Plasma MNs exhibited a superior sensitivity than 24-h-urinary CAs in the Chinese PPGL diagnosis. Patients with a small tumor, normal blood pressure and negative 131I-MIBG imaging were prone to express negative biochemical levels. Additionally, an obvious elevation of 24-h-urinary CAs than plasma MNs was correlated to paroxysmal hypertension and the Epinephrine type.

Visfatin and VEGF levels are not increased in adolescent girls with polycystic ovary syndrome

IntroductionPCOS is one of the most commonly occurring endocrinopathies among women and increasingly affects adolescent populations. The connection between PCOS and various endocrinological, psychological, and CVD is increasingly recognized. Some studies have shown elevated levels of visfatin and VEGF among patients with PCOS, which are markers of vascular endothelial dysfunction. In our study, we evaluated the concentration of these parameters, focusing solely on a group of adolescents with PCOS, to assess whether these early markers of CVD are present at an early stage of diagnosis.Material and methodsIn total, 80 adolescent girls participated in the study. 47 adolescents diagnosed with PCOS were included in the study group (mean age 15.68 ± 1.18 years, BMI 26.66 ± 6.41 kg/m2), while the remaining 33 regularly menstruating individuals (mean age 15.79 ± 1.22 years, BMI 25.44 ± 7.24 kg/m2) were assigned to the control group. Each participant underwent imaging, biochemical, and hormonal tests. Additionally, markers of endothelial dysfunction: VEGF and visfatin, were measured in all adolescents.ResultsBoth VEGF and visfatin levels did not differ significantly between PCOS and control group (p=0.30 and p=0.15, respectively). In the group of adolescent girls with PCOS, visfatin was significantly correlated with HDL, FSH, cortisol, and testosterone levels &amp;gt;55 ng/dl. VEGF was significantly correlated with fasting glucose, glucose levels after OGTT, estradiol, and waist circumference &amp;gt;80 cm.ConclusionIt can be indirectly inferred that both visfatin and VEGF should not be used as early markers for cardiometabolic complications among adolescent patients with PCOS. On the other hand, low visfatin levels, through their negative correlation with HDL, may have a protective effect on cardiovascular complications, while low VEGF levels, through their positive correlation with glucose levels, may have a protective influence on carbohydrate metabolism disorders.

MÉTODOS DE DIAGNÓSTICOS DE HIPERADRENOCORTICISMO EM CÃES UMA REVISÃO NARRATIVA

The objective of this research was to investigate and evaluate the diagnostic methods used for hyperadrenocorticism in dogs by analyzing the available literature from the past 20 years. The methodology employed was a qualitative and exploratory literature review, conducted through databases such as PUBMED, MEDLINE, BVS, SCOPUS, PERIÓDICOS, BIBLIOTECA ABERTA USP, and SCIELO. Keywords such as "dogs," "canine," "hyperadrenocorticism," "endocrine," "endocrinopathy," and "Cushing" were used to identify relevant studies. The content analysis of the selected articles revealed that diagnostic methods vary according to the clinical suspicion and include detailed anamnesis, thorough clinical examination, and basic and imaging laboratory tests. The choice between suppression and stimulation hormone tests depends on the suspected origin of the condition, with the low-dose dexamethasone suppression test being highly sensitive for detecting hyperadrenocorticism, while the ACTH stimulation test is crucial for differentiating between origins. Diagnostic confirmation also involves abdominal ultrasonography to visualize the adrenal glands and identify possible masses, which is essential for guiding appropriate treatment and determining the patient’s prognosis.

Testosterone to Estradiol Ratios in Fertile and Subfertile Men: A Large Cohort Analysis

ObjectiveTo validate the established normal testosterone to estradiol ratio and characterize the distribution of testosterone to estradiol ratios in a large cohort of fertile and subfertile men. Materials and MethodsRetrospective review of adult men (≥18 years of age) presenting for fertility evaluation between 2002 and 2021 who underwent evaluation by a reproductive urologist, had two separate semen analyses and had hormonal testing within six months of their index semen analysis. Men were dichotomized into fertile and subfertile groups based on total motile sperm count on two semen analyses. The subfertile cohort included men with a total motile sperm count <20 million on both semen analyses. The main outcome measures were serum testosterone, serum estradiol, and serum testosterone to estradiol ratio. ResultsAmong 816 men, 651 (79.8%) were classified as fertile and 165 (20.2%) as subfertile. Median testosterone (ng/dL) to estradiol (pg/mL) ratios were similar between the groups (14.48 vs 15.00, p=0.5). The 20th percentile testosterone to estradiol ratio for the fertile group was 9.77. ConclusionsThis is the largest study to date characterizing testosterone to estradiol ratios in men presenting for fertility evaluation. We validated the 10/1 ratio that was previously established as the 20th percentile for fertile men. We found no difference in testosterone to estradiol ratios between fertile and subfertile men defined by total motile sperm count, highlighting the need for further investigation to better define the cohort of men with infertility who could benefit from aromatase inhibitor therapy.

Immunocastration caused dysfunction of Père David’s deer (Elaphurus davidianus)

Abstract The population density of Père David’s deer (Elaphurus davidianus) in Jiangsu Dafeng Milu Nature Reserve was excessively high due to an overemphasis on population recovery, while ignoring the crucial relationship between population size and habitats. This study used immunocastration to capture four Père David’s deer and observed their behavior. Their blood was collected for sex hormone testing, transcriptomics, and metabolomics analysis. In addition, six uncastrated Père David’s deer were included as control group. The results showed that reproductive behavior was absent in castrated Père David’s deer, while castrated individuals exhibited a significant decrease in blood hormone testosterone concentration compared to uncastrated Père David’s deer. Transcriptome and metabolome analyses revealed 450 differentially expressed genes (DEGs) and five differentially expressed metabolites (DEMs), Combined analysis of transcriptome and metabolic data revealed a significant correlation between DEGs and DEMs. It shows that using immune castration to control the population of Père David’s deer may disrupt their cell apoptosis and disturb the cell cycle, leading to abnormal pathways and promoting the onset of many diseases. Therefore, a cautious approach should be adopted toward immune castration as a means of population control. This study can provide valuable references for the standardized management of Père David’s deer populations.

Psychological Impact of Presymptomatic X-Linked ALD Diagnosis and Surveillance: A Small Qualitative Study of Patient and Parent Experiences

X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder. Symptoms range from cerebral demyelination (cALD) to adrenal insufficiency and slowly progressive myeloneuropathy. cALD is fatal if not treated with hematopoietic cell transplantation in the early stages of the disease course. This can be achieved through cascade testing or newborn screening (NBS). Due to the lack of predictive measures of disease trajectory, patients are monitored with frequent MRI scans and hormone testing to ensure timely intervention. With this study, we wanted to explore how the diagnosis of ALD, before the development of cALD, and the follow-up program affected patients and their parents. Using semi-structured interviews, we interviewed seven parents of children with ALD aged 3–11 and four patients with ALD aged 18–25. Because NBS for ALD has not been implemented in Denmark, the patients were identified through either cascade testing or after having presented with adrenal insufficiency. We generated five themes: (I) ALD patients maintained mental resilience despite diagnosis and surveillance; (II) patients’ concerns matured with age and centered around situations that confronted them with their patient status; (III) parents of children with ALD had both short-term and long-term worries for their children’s health; (IV) parents took on a huge psychological burden; and (V) due to its rarity, the diagnosis of ALD evoked a sense of isolation and disease-related loneliness. Overall, we found a large discrepancy in the experiences reported by parents and patients. Despite the small sample size, we identified patterns that suggest that while the early diagnosis took a significant psychological toll on the parents, patients lived relatively carefree lives despite their ALD diagnosis.

An Update on Advances in Hypopituitarism: Etiology, Diagnosis, and Current Management.

This article provides an updated review of hypopituitarism (HP), an endocrine disorder characterized by a deficiency of one or more pituitary hormones. The various etiologies are reviewed, including pituitary neuroendocrine tumors (PitNETs), hypothalamic lesions, genetic mutations, and acquired factors such as head trauma, medications, neoplasms, and infiltrative diseases. It is noted that PitNETs are responsible for approximately half of the cases in adults, whereas in children the causes are predominantly congenital. Diagnosis is based on clinical evaluation and hormonal testing, with identification of the specific hormonal deficiencies essential for effective treatment. Laboratory tests present challenges and limitations that must be understood and addressed. Hormone replacement therapy is the mainstay of treatment, significantly improving patients' quality of life. It is important to know the possible interactions between hormone replacement therapies in HP. Recent advances in understanding the pathophysiology of HP and the importance of a multidisciplinary approach to the management of associated complications are discussed. This article emphasizes the need for comprehensive evaluation and continuous follow-up to optimize outcomes in patients with HP and highlights the importance of ongoing research to improve diagnostic and treatment strategies.

Respiratory failure and rhabdomyolysis caused by severe hypokalemia in a young female with hypertension: a rare critical condition in primary aldosteronism

BackgroundThe two classic manifestations of primary aldosteronism are hypertension and hypokalemia. However, acute respiratory failure due to hypokalemia in primary hyperaldosteronism is rare.Case presentationThe patient was a 27-year-old female who presented with drowsiness and weakness in all extremities. She had been diagnosed with hypertension three years prior, with irregular follow-up, and had a history of preeclampsia one year later. She exhibited high blood pressure and severe hypokalemia (2 mEq/L), leading to respiratory depression and impending respiratory arrest. Consequently, the patient was intubated and transferred to the intensive care unit (ICU). She also developed rhabdomyolysis. Blood pressure tests, including hormonal tests (aldosterone: 13.2 ng/dL, plasma renin activity: 0.32 ng/mL/h), were conducted. Due to the high aldosterone-renin ratio, an abdominopelvic computed tomography (CT) scan was performed. The CT scan revealed a 14 × 12 mm round mass with a washout value above 60%, consistent with an adrenal adenoma, leading to a diagnosis of primary aldosteronism. The patient was discharged after stabilization, and one and a half months after ICU admission, a laparoscopic left adrenalectomy was successfully performed without post-operative complications. Histopathology showed encapsulated hypertrophy of the adrenal cortex with a predominance of large clear cells, confirming the diagnosis of adrenal adenoma. At the most recent follow-up, the patient had normal potassium levels, was normotensive without any medications, and exhibited no alarming signs or symptoms.ConclusionRespiratory depression to the extent of impending respiratory failure and rhabdomyolysis as a result of hypokalemia in primary aldosteronism are extremely rare. In this patient, who developed respiratory depression due to resistant hypokalemia, timely investigation of secondary causes and diagnosis of adrenal adenoma were crucial. The surgery provided definitive treatment for the patient’s blood pressure and prevented the recurrence of life-threatening complications.

Immunohistochemical expression of CYP11A1, CYP11B, CYP17, and HSD3B2 in functional and nonfunctional canine adrenocortical tumors.

Functionality of human adrenal tumors is inferred by CYP11B1 (cortisol synthase) expression, CYP11B2 (aldosterone synthase) expression, or both. Nonfunctional canine adrenal tumors have low expression of steroidogenic enzymes, whereas aldosterone-producing tumors express CYP11B, and cortisol-producing tumors express both CYP11B and CYP17. Twenty-two client-owned dogs with adrenocortical tumors (ACT) (8 nonfunctional, 7-cortisol producing, 2 aldosterone-producing and 5 functional noncortisol producing) and 2 dogs with normal adrenal glands. Retrospective case series. Adrenal functionality was determined from clinical signs and endocrine testing. CYP11A1, CYP11B, CYP17, and HSD3B2 expression was detected by immunohistochemistry on formalin-fixed paraffin-embedded adrenal tissue. Protein expression was semiquantified by 2 blinded observers using H-scoring (results reported as median [range]) and compared in nonfunctional and cortisol-producing adrenal tumors by Mann-Whitney U tests. CYP11A1, CYP11B, and HSD3B2 were present within all cortical layers of normal adrenal glands, and CYP17 was expressed within the zona fasciculata and zona reticularis. Expression of CYP11A1 (191.25 [97.5-270] vs. 175 [102.5-295] P = .69), CYP11B (190 [130-265] vs. 147.5 [95-202.5]; P = .07), CYP17 (177.5 [87.5-240] vs. 247.5 [55-292.5]; P = .40), and HSD3B2 (230 [47.5-295] vs. 277.5 [67.5-295]; P = .34) were not significantly different between cortisol-producing and nonfunctional ACT. Our findings suggest it is not possible to determine functionality of canine ACT by immunohistochemistry for steroidogenic enzymes. Tumor size cannot be used to infer functionality of adrenal tumors.

Helping Patients to Predict and Confirm Ovulation with the Use of Combined Urinary Hormonal and Smartphone Technology: A Proof-of-Concept Retrospective Descriptive Case Series.

Smartphone-based fertility awareness methods with home-based urinary hormonal testing are gaining popularity for fertility tracking. In our university-affiliated family practice, we integrated a previously developed ovulation tracking application into a protocol for monitoring urinary sex hormones and cervical secretions. Serum progesterone was used to confirm the luteal phase, with levels ≥ 15.9 nmol/L ensuring confirmation. Data from 110 women seen for infertility treatment (n = 95) or family planning advice (n = 15) and using our ovulation prediction protocol showed that most opted for a combination of cervical mucus and luteinizing hormone testing (n = 86). Among those using it for family planning, the median usage among women spanned 56 cycles, and 13 cycles per woman required progesterone testing for confirmation. Thirteen patients are still using the method without unintended pregnancies. No unintended pregnancies occurred. Confidence in tests based on serum progesterone was high (93%). For infertility, the method helped in the identification of anovulation, evaluating treatment response, and in diagnosing subfertility causes. This proof-of-concept retrospective descriptive case series suggests the potential for smartphone-based monitoring in fertility management, urging further studies for application enhancements and prospective validation.

Acromegalia em felinos

Acromegaly in felines occurs mainly due to a pituitary adenoma of somatotropic cells, and presents slow and progressive evolution, responsible for increasing the production and secretion of growth hormones (GH). This condition is common in senile or adult male domestic cats, neutered and with short hair. The pathophysiology is due to the excessive release of GH in the adenohypophysis region, whose synthesis is regulated by growth hormone-releasing hormone (GHRH) and somatostatin, responsible for stimulating or inhibiting the secretory axis, respectively. The anabolic action of GH is responsible for increasing the secretion of IGF-1, which is mainly responsible for the clinical signs of acromegaly, such as body growth and organomegaly. The catabolic effect refers to insulin resistance. Clinical signs may be associated with secondary diabetes mellitus (DM), weight gain, exacerbated growth of various tissues and neurological signs as the tumor mass grows. The diagnosis of the disease can be performed through laboratory, imaging and endocrine tests such as the specific immunoassay for GH and/or insulin-like growth factor 1 (IGF-1). Treatment is based on controlling the DM that develops secondary to it, as well as on attempts to reduce or even inhibit the excess release of GH. Treatment can be performed with somatostatin analogues and dopamine agonists. The use of stereotactic radiotherapy can also be recommended, with favorable results for tumor reduction, as well as the surgical technique of transsphenoidal hypophysectomy, which presents better results than other techniques but is a complex surgical procedure. This project aims to inform veterinarians of this endocrine disease and its main currently recognized diagnoses and treatments, emphasizing the need to establish a differential diagnosis for difficult-to-control DM.

8204 Rare Asymptomatic Presentation Of A Large Pheochromocytoma

Abstract Disclosure: A. Lorin: None. C.K. Persaud: None. M.H. Kemm: None. Background: Pheochromocytoma is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. It is associated with excessive release of catecholamines causing symptoms of hypertension, palpitations, diaphoresis, and headaches. These symptoms are particularly prominent with larger pheochromocytomas. We present the case of a large 13 cm pheochromocytoma (PCC) without the typical associated symptoms. Clinical Case: A 45-year-old male with medical history of osteoarthritis and gastroesophageal reflux presented to his primary care doctor with 2 months of intermittent right upper quadrant abdominal pain associated with nausea. Work up with CT abdomen/pelvis found a 9.3 cm heterogeneous right adrenal mass with mass effect on the right liver lobe, superior pole of the right kidney, duodenum, and pancreatic head. Hormonal testing was notable for plasma metanephrine 257.8 pg/mL (0-88), plasma normetanephrine 12063.7 pg/mL (0.0-218.9), 24 hr urine metanephrine 159 mcg/24 hr (58-276), 24 hr urine normetanephrine 22575 mcg/24 hr (156-729), and chromogranin A 5387 mg/mL (0-101.8). Given lab evaluation, diagnosis was made of pheochromocytoma, and patient was initiated on alpha blockade with doxazosin. Patient’s blood pressure and heart rate were at goal prior to doxazosin initiation and patient needed to be decreased from 1 mg daily to 0.5 mg daily due to side effects of low blood pressure and orthostatic hypotension. Patient had an uncomplicated open right adrenalectomy with pathology showing a 13 cm pheochromocytoma with invasion through the capsule into the periadrenal adipose tissue. Genetic testing revealed no known mutation variants associated with PCC. Labs drawn two weeks postoperatively showed resolution of elevated plasma metanephrine, normetanephrine, and chromogranin A. Conclusion: While the patient had an elevated plasma metanephrine, the normetanephrine was predominantly elevated. Such a hormone profile is more common in extra-adrenal PCCs, consistent with cluster 1 associated genes. This noradrenergic phenotype is likely a reason the patient did not have typical symptoms, despite the size of his pheochromocytoma. A proposed pathophysiologic mechanism for this is the dissociation of renal medulla from the cortex given the large size of the tumor. This would lead to lower local availability of corticosteroid to potentiate the conversion of norepinephrine to epinephrine, thus decreasing likelihood of classical PCC symptoms. Despite lack of expected symptoms and an imaging initially concerning for adrenocortical carcinoma, we should recognize the potential for a large adrenal tumor to represent PCC and evaluate accordingly. Presentation: 6/1/2024

7756 Gonadectomy in Individuals with Differences of Sex Development - A Prospective I-DSD Registry Study

Abstract Disclosure: M.A. O'Connell: None. A.K. Lucas-Herald: None. J. Bryce: None. M. Chen: None. J.H. Davies: None. M. Shnorhavorian: None. N. Atapattu: None. I. Bachynska: None. N. Birkebaek: None. M. Cools: None. K. Demir: None. L. de Vries: None. H. Elsedfy: None. M.A. Fahmy: None. E. Globa: None. R. Grinspon: None. G. Guaragna-Filho: None. G. Guerra-Junior: None. D. Janus: None. Z. Kolesinska: None. I. Mazen: None. S.M. O'Connell: None. S.N. Seneviratne: None. M. Stancampiano: None. G. Verkauskas: None. S.F. Ahmed: None. O. i-DSD gonadectomy surveillance consortium: None. Introduction: Gonadectomy may be indicated in people with differences of sex development (DSD), but variation in practice is reported. This study aims to determine, through prospective surveillance, the frequency of gonadectomy and associated care pathways in individuals with DSD internationally. Methods: All I-DSD centres were invited to participate; the study commenced in December 2022. Participating centres receive a monthly email asking whether a gonadectomy has been performed in an individual with DSD. Where informed consent for inclusion in the I-DSD Registry has been obtained in a reported case, a secondary survey captures additional clinical information. Results: Of 208 centres invited, 74 have responded to monthly email surveys. Over the first 12 months of surveillance, gonadectomies were reported in 71 individuals from 34 centres in 19 countries (median [range]: 1[1, 5]); 40 centres reported no gonadectomy. Secondary survey data are available for 30/65 (46%) of reported cases to date. Twenty-four (80%) individuals are female; median (range) age at gonadectomy was 9.2 (2.1,20.0) years. All had specialist multidisciplinary team involvement prior to gonadectomy: endocrinology (97%), genetics (77%) and psychology (67%) were most frequently involved. Gonads were intra-abdominal in 25/30 (83%). Differences of gonadal development (13/30 [43%]) and Turner syndrome (8/30 [27%]) were the most frequent underlying DSD. Pre-gonadectomy investigations included: hormonal testing (28/30 [93%]), imaging (23/30 [77%] - US alone n=14; US + MRI n=7; MRI alone n=2), direct visualisation at laparoscopy (7/30 [23%]) and gonadal biopsy (2/30 [7%]). Bilateral gonadectomy was undertaken in 25/30 (83%). Mitigation of future malignancy risk in the context of gonadal insufficiency was the most common primary indication for gonadectomy (19/30, [63%]); additional indications were concerning changes on biopsy/imaging (3/30 [10%]), hormone production incongruent with sex assigned (4/30 [13%]) or gender identity (2/30 [7%]) and parental choice (2/30 [7%]). Histopathology confirmed neoplastic change in 7 individuals (23%). Gonadectomy was intentionally deferred in 8/30 (27%) individuals, most commonly to allow their involvement in decision making. Twelve individuals (40%) were 12yrs or older at gonadectomy; all were involved in the pre-operative decision-making process. Conclusions: This study offers important contemporary insights into the practice of gonadectomy in individuals with DSD internationally. Multidisciplinary care provision prior to gonadectomy is standard; however, management pathways vary, likely reflecting diversity of clinical presentations and lack of consensus regarding optimal approach. The I-DSD platform shows clear utility for performing prospective surveillance of rare procedures; such studies are essential for care quality improvement. Presentation: 6/2/2024

9234 A Case of Gigantism Due to An AIP Gene Mutation: Implications for Genetic Counseling and Preimplantation Genetic Diagnosis

Abstract Disclosure: M. Serebro: None. M. Yacobi Bach: None. N. Even Zohar: None. A. Reches: None. Y. Greenman: None. From the age of 17 the patient experienced accelerated growth, facial changes, and enlargement of hands and feet. Despite having a sister already diagnosed with acromegaly, the patient did not undergo endocrine evaluation until the age of 25, when he was diagnosed with gigantism. Magnetic resonance imaging (MRI) revealed the presence of a macroadenoma with suprasellar extension reaching the optic chiasm. The patient underwent transsphenoidal surgery and excision of a sparsely granulated somatotroph adenoma that was Pit1 positive and exhibited weak immunostaining for growth hormone (GH). Insulin-like growth factor 1 (IGF1) levels normalized after surgery, and a fasting GH level was 0.6 ng/ml. Given the family history and the early onset of the disease, genetic counseling was recommended. Genetic testing revealed a heterozygote likely pathogenic variant in the AIP gene (c.713G&amp;gt;A). This finding prompted the recommendation for genetic testing of all first-degree relatives. The patient and his wife, who desired to have children, were referred to obstetrics and gynecology for pregestational diagnosis. Family segregation testing indicated that the patient's mother also carried the same AIP variant. Preimplantation genetic diagnosis (PGD) was conducted, revealing that 11 out of 20 embryos were carriers of the AIP variant. The non-carrier embryos were selected for implantation, and pregnancy was achieved. Efforts to inform first-degree relatives about the importance of genetic testing were undertaken, and one sister was tested and found to be healthy. Other siblings have not yet been tested. The patient's mother, identified as an AIP variant carrier, underwent endocrine laboratory tests that showed GH, IGF1, and prolactin levels within the normal range. Brain MRI did not reveal a pituitary lesion.This case highlights the significance of genetic counseling and testing in patients with familial endocrine disorders, the potential implications of a molecular diagnosis of a pathogenic AIP variant, and the challenges faced in reproductive decision-making for affected individuals and their families. Presentation: 6/3/2024

7192 Description Of Patients With Post-surgical Hypoparathyroidism In Clinical Follow-up In Brazil

Abstract Disclosure: L.D. Santos: None. G. Oliveira Martins: None. L. Costa Figueiredo: None. M. Nascimento de Lemos: None. J.V. Lima: None. L.A. Alvares: None. E.N. Sakane: None. N. Scalissi: None. Post-surgical hypoparathyroidism is an event that may occur, especially after extensive procedures in the cervical region. There are few long-term follow-up studies on individuals who develop permanent post-surgical hypoparathyroidism and its long-term complications. Objective: This study aims to assess the clinical and laboratory characteristics of patients diagnosed with permanent hypoparathyroidism at a tertiary care center in Brazil. Methods: We conducted a retrospective analysis of medical records. Results: We evaluated 27 patients with permanent hypoparathyroidism, with an average age of 53 years (SD=10), where 15% were alcohol and tobacco consumers, and 88% were female. The average time of permanent hypoparathyroidism diagnosis was 9 years and 3 months. Regarding the surgical indication, 35% were due to Graves' disease, 25% for thyroid goiter, 25% for thyroid cancer, and 15% for glottic cancer. Only 15% had a description of the parathyroid glands in the pathology report. As for medications, all patients were using calcium carbonate, with an average dose of 1700 mg daily per individual. 90% of the patients were using calcitriol, with an average dose of 0.64 mcg daily, and 55% were using cholecalciferol, with an average weekly dose of 9700 IU. Hydrochlorothiazide was used by 35% of the patients, with an average daily dose of 34 mg. Regarding postoperative exams 24 hours after surgery, only half had the parathyroid hormone (PTH) test requested or available, with only one patient having PTH &amp;gt;10 pg/mL. Regarding chronic complications, 15% presented with nephrolithiasis, 5% with subcapsular cataract, 5% with prophylaxis for seizures, 15% with a diagnosis of depression, and 10% with arrhythmias. Conclusion: Individuals with permanent hypoparathyroidism require attention due to chronic complications, and proper treatment aims to reduce the chance of developing other diseases associated with permanent post-surgical hypoparathyroidism. Presentation: 6/2/2024

7337 High Parathyroid Hormone (PTH) Due To Immunoassay Interference

Abstract Disclosure: V.A. Mendpara: None. A.J. McShane: None. L.Z. Khan: None. Background: PTH levels are not always accurate. This case illustrates immunoassay interference in a female with markedly abnormal PTH values. Understanding immunoassay interference in diverse hormonal assessments can prevent diagnostic inaccuracies. Clinical Case: A 63-year-old female with osteopenia underwent serum parathyroid hormone (PTH) testing as part of a thorough bone evaluation. The initial PTH level revealed an abnormal level of 4008 pg/mL (normal range: 15 to 65 pg/mL). The follow-up PTH level with the same assay continued to result in elevated values of &amp;gt;5000 pg/mL. The medication list was negative for biotin use, which is a well-known interfering substance in the PTH assay. Clinical evaluation was negative for hyperparathyroidism symptoms, and thyroid/parathyroid ultrasound was normal, as were serum levels of phosphate, vitamin D, and calcium. No PTH values had been checked for patients in the past after an extensive review of prior records. The initial PTH testing used the Roche Elecsys PTH STAT assay. To investigate a potential immunoassay interference, the following studies were performed: First, the sample was diluted with polyethylene glycol (PEG) to precipitate large molecular weight proteins; second, the sample was treated with a commercial heterophilic blocking reagent (Scantibodies Laboratory); and lastly, the sample was assayed utilizing a different PTH vendor (Siemens Atellica, chemiluminescent immunoassay). The PEG and heterophilic blocking treatments resulted in significantly lower PTH concentrations of 895.6 and 40.7 pg/mL, respectively. We do not anticipate a change in PTH levels in samples supplemented with blocking reagents or PEG without interference. The result from Siemens’ assay was markedly lower at 43.4 pg/mL. Both the Siemens and Roche assays employ mouse antibodies; however, the antibodies are proprietary between the vendors. This results in potentially different anti-mouse antibody epitope targets. Due to a history of advanced ovarian cancer, the patient was taking Oregovomab, a murine monoclonal antibody, as therapy for her advanced disease. It is unclear if this medication resulted in assay interference, but it is possible. Discussion: In summary, the discrepancy in PTH assay results highlights the need to consider immunoassay interference, particularly in patients with a history of cancer on immunotherapy agents. Our case highlights the importance of the clinician’s review of medications when assessing patients. While prior PTH assays were not conducted before the patient started Oregovomab, the potential development of interfering antibodies warrants consideration. Clinicians should be vigilant for atypical results and collaborate closely with laboratory professionals, as detecting interfering substances can result in misdiagnosis. Presentation: 6/2/2024

7308 A Case of Thyroid Hormone Resistance Associated With a Novel Mutation in the THRA Gene

Abstract Disclosure: J.A. Siddiqui: None. M. Barbosa: None. V. Fettig: None. C.J. Romero: None. Introduction: Thyroid hormone resistance (THR) is a syndrome leading to decreased response of target organs to thyroid hormone. Normal thyroid hormone action is mediated by thyroid hormone nuclear receptors and is essential for normal development and metabolism. Two isoforms are encoded by the thyroid hormone receptor α and β genes (THRA and THRB). Mutations in THRB are commonly reported with limited cases of THRA mutations. We report a 15-month-old and her mother with a pathogenic variant in the THRα receptor leading to thyroid hormone resistance. CASE: A 15-month-old ex-39-week gestation female was born small for gestational age (birth weight: 2450 grams,3rd %ile and birth length: 17 inches,1st %ile). The newborn screen was normal. She presented with macroglossia, low tone and global developmental delay. She had severe constipation complicated by rectal prolapse that required surgical correction. There are multiple relatives (mother, maternal half-brother and maternal grandparents) with neurodevelopmental issues. The mother’s previous genetic evaluation was non-diagnostic. Mother reports a thyroid condition but without treatment. The patient was initially referred to genetics and whole exome sequencing revealed a heterozygous c.1205 T&amp;gt;C p. (L402P) variant in the THRα gene, which was maternally inherited and reported as a variant of uncertain significance. On physical exam, Heart rate was 112 bpm; height &amp;lt;1%ile (Z-score -3.22 SD), weight 3%ile (Z-score -1.89 SD). Patient has a wide anterior fontanelle (4x3 cm), macroglossia and delayed teeth eruption. Other exam findings: non-palpable thyroid and postaxial polydactyly on the 5th digit of the right toe. Thyroid hormone testing: normal TSH 1.829 uIU/mL, low total T4 4.4 mcg/dL, low Free T4 of 0.58 ng/dL and high free T3 of 4.24 pg/mL. Levothyroxine treatment was initiated(25 mcg daily). After 1 month treatment, TSH level was 0.23 uIU/mL, total T4 was 6.1 mcg/dL and low reverse T3 of 5.8 ng/dL. DISCUSSION: Thyroid hormone resistance due to THRα mutations are rare and under-recognized. The main clinical phenotype includes growth retardation, delayed development, decreased muscle tone, delayed tooth eruption and constipation. Unlike patients with THRβ mutations, the hypothalamus-pituitary-thyroid axis in patients with THRα mutations is minimally affected with a normal TSH level. Total T3 levels are elevated with slightly low total T4 and free T4:T3 ratio is low. Treatment with levothyroxine leads to suppressions of TSH levels, therefore confirming intact central T3 feedback loop. Reports, however, show minor clinical improvements with treatment; therefore further research is needed in these patients to explore more effective therapeutic options. We present a case of a novel congenital THRA mutation leading to a clinical phenotype consistent with THR. She continues care in our clinic with hopes to further study her mutation. Presentation: 6/2/2024

8138 Pituitary Stalk Interruption Syndrome (PSIS) in a patient with Isolated Hypogonadotropic Hypogonadism

Abstract Disclosure: A. Thomson: None. R. Osman: None. Pituitary Stalk Interruption Syndrome in a Patient with Isolated Hypogonadotropic Hypogonadism Pituitary Stalk Interruption syndrome (PSIS) is a rare cause of hypopituitarism, characterized by a radiologic constellation of thin or interrupted pituitary stalk, hypoplasia, or aplasia of the anterior lobe and with the presence of an ectopic posterior pituitary (EPP). It is most commonly associated with isolated growth hormone deficiency (IGHD) and is often diagnosed in childhood. We present one case of a patient with isolated hypogonadotropic hypogonadism in adulthood, subsequently found to have an PSIS on MRI. A 45 year old male patient presented to our clinic with hypogonadism. He gradually started developing decreasing libido, fatigue, and loss of erections. He had normal puberty and childhood growth, and has fathered one child. He denied history of anosmia or visual symptoms. Subsequent hormonal testing showed: morning Total Testosterone: 145 ng/dl (normal 264-916 ng/dl), Free testosterone 1.5 pg/ml (normal 6.8-21.5 pg/ml), LH 1.1 mIU/ml (normal 1.7-8.6 mIU/ml) and FSH of 3.6 mIU/ml (normal 1.5-12.4 mIU/ml). Prolactin was minimally elevated at 21 ng/ml (normal 4.0 - 15.2 ng/ml). Thyroid, IGF-1, cortisol, and ferritin levels were within normal limits. Repeat levels showed similar findings. He denied ever taking any form of exogenous testosterone. His pituitary MRI revealed a small volume of anterior pituitary tissue, measuring 0.2cm x 0.7cm x 0.7cm, without discrete pituitary adenoma, a hypoplastic midline stalk measuring 1.3 mm in AP diameter (nl 2-3 mm), with a T1 hyperintense nodularity measuring 0.6cm x 0.4cm along the posterior aspect of the sella turcica consistent with EPP. No additional structural abnormality or any mass lesions were identified. He was subsequently started on replacement testosterone therapy and his symptoms resolved. PSIS usually presents in childhood with IGHD. Patients may have other pituitary hormone deficiencies and congenital central nervous system defects, although panhypopituitarism is rare. There have been reports in children with delayed puberty and isolated hypogonadotropic hypogonadism who have been found to have PSIS. Only one othercase of an adult female patient exhibiting hypogonadotropic hypogonadism as the only manifestation of PSIS has been documented in the literature. Our case highlights the potential for an adult male to present later in life with hypogonadotropic hypogonadism as a manifestation of PSIS. The marginally elevated prolactin level may be due to lack of inhibition of hypothalamic dopamine on lactotroph cells within the pituitary caused by the EPP, although it is doubtful that this has clinical significance. This is a rare presentation of PSIS, clinicians should be mindful ofthis radiological constellation and the potential for isolated hypogonadotropic hypogonadism presenting unusually in the adulthood. Presentation: 6/3/2024

12573 Management Challenges In A Young Male With Bilateral Macronodular Adrenal Hyperplasia

Abstract Disclosure: C. Nguyen: None. V. Ghernautan: None. L.Y. Melendez-Ramirez: None. M.C. Chiang: None. D. Lovre: None. Bilateral adrenal hyperplasia (BAH) may present in isolation or as part of a syndrome. It is classified according to nodule size as Macronodular: primary bilateral macronodular adrenal hyperplasia (PBMAH), or Micronodular: primary pigmented micronodular adrenal hyperplasia (PPNAD) and isolated micronodular adrenal hyperplasia (iMAD). High variability in cortisol secretion and disease progression is seen in both forms subclinical and overt Cushing’s Syndrome (CS). In PBMAH, bilateral adrenalectomy is advised for remission of CS, but benefits must be weighed against risks of lifelong adrenal insufficiency. A 45-year-old male with hypertension, depression, prediabetes, obesity presented to clinic for second opinion regarding incidentally discovered adrenal nodules five years prior with negative initial hormonal workup. Over the previous year he had gained 20 lbs. and developed proximal muscle weakness and sleep apnea. Physical exam showed uncontrolled hypertension and increased abdominal and supraclavicular fat. Hormonal testing revealed hypercortisolism. Adrenal CT confirmed bilateral adrenal nodules up to 4.9 cm with absolute washout ≥60% consistent with benign etiology. CS secondary to PBMAH was diagnosed. Prior to surgical evaluation. Ketoconazole 200 mg twice daily was started and titrated to 400 mg twice daily over the next three months. ACTH became detectable and symptoms of hypercortisolism improved. Right adrenalectomy was performed. Surgical pathology showed golden yellow-orange nodules with minimal grey adrenal parenchyma without necrosis or hemorrhage. The gland was 9.5 x 5.8 x 2.6 cm and weighed 85 g. Microscopic examination showed macronodular hyperplasia. Following surgery, he experienced a 17-pounds weight loss, improvement in blood pressure and quality of life. Three months later, hypercortisolism recurred. He elected to be monitored clinically and contemplating option of left adrenalectomy.Our case highlights the challenges in the care of patients with PBMAH. Bilateral adrenalectomy (BA) is the classical treatment. Its disadvantages include life-long hormone replacement with risk for adrenal crisis, increased morbidity, and mortality. Surgical alternatives, such as unilateral adrenalectomy (UA) and UA with subtotal contralateral adrenal resection, have shown promising results with up to 90% remission rates. The role of adjuvant novel medical therapy is unknown. Studies to compare cost, quality of life, cardiovascular risk, comorbidities, and life span between BA and UA are lacking. New biomarkers are needed to allow closer monitoring of disease progression. Additional research is necessary on medical management of hypercortisolism recurrence after UA and its long-term safety. Finally, given the presence of germline defects associated with adrenal hyperplasia, genetic testing should be offered to all patients with BAH. Presentation: 6/1/2024

7407 Normosmic Idiopathic Hypogonadotropic Hypogonadism in Women: A Case Report and Comprehensive Review

Abstract Disclosure: E.G. Bustamante: None. M. Sulehri: None. I. Patoli: None. A. Karunakaran: None. Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH) in Women: A Case Report and Literature ReviewIntroduction: IHH is a rare genetic disorder affecting gonadotropic-releasing hormone (GnRH) production and/or action, resulting in diminished sex steroid levels. Characterized by the absence of spontaneous pubertal development. In women, it manifests with normal adrenarche but absent thelarche and menarche. Our case highlight a late diagnosis of IHH in a 34-year-old woman with primary amenorrhea. Case report: A 34 year old lady with a history of primary amenorrhea sought evaluation. At age 16, she underwent assessment for short stature and primary amenorrhea, denying anosmia, headache, visual disturbances. Evaluation revealed bone age concordant with chronological age and normal MRI Brain. Pelvic ultrasound (US) showed small premenarchal uterus and ovaries. She initiated oral contraceptive pills (OCP) and experienced regular menses. Seeking fertility assistance at age 24, a normal Hysterosalpingogram was followed by successful delivery of twins after ovarian stimulation. Post-delivery menses did not resume and OCP was not restarted. Family history revealed a sister with irregular periods requiring OCP.Subsequently workup at age 30 showed Estradiol 22 pg/ml, FSH/LH 4.1/2.3 mUI/mL; normal PRL, TFT, DHEAS, 17OHP. Repeat Pelvic US showed normal uterus, endometrial stripe normal at 0.24 cm and non-visualized ovaries. PCOS testing negative for hyperandrogenism. Progesterone challenge resulted in no withdrawal bleeding. Brain MRI demonstrated a 2.2 x 1.3 mm hypoenhancing ovoid mass in the pars Intermedia of the pituitary gland suggestive of pituitary microadenoma. Pituitary axis hormonal testing was normal. Karyotype revealed 46 XX (normal female). Genetic evaluation identified a pathogenic variant (p.R35C) in GNRH1 gene. Her final diagnosis: nIHH. Discussion HH is diagnosed in 5% of all women with primary amenorrhea and is divided into 2 major categories: Kallmann syndrome and nIHH. The majority of known causes of HH can be attributed to mutations in KAL1, FGFR1, or GNRHR. The p.R35C variant has been associated with autosomal dominant nIHH. Diagnosis involves clinical suspicious, low LH/FSH and sex steroid levels, normal hypothalamic–pituitary imaging, and exclusion of differentials.Treatment goal for female focus on regular breast and uterine development, as well as the capability to conceive. Use of hormonal replacement therapy and/or gonadotropins or pulsatile GnRH for ovarian stimulation are essential. ConclusionWhile IHH predominantly affects men, limited literature explores its manifestation in women and its impact on fertility. The identification of a GNRH1-related nIHH variant highlights the role of genetic testing in specific HH diagnoses. Failure to diagnose in adolescence may compromise women overall well-being Presentation: 6/1/2024